Background and Aim: Stigmas of Crocus sativus L. is widely used against different human diseases.Regarding the properties of this plant, in the present study the effects of saffron extract on inducing cell differentiation of a rat's bone marrow-derived mesenchymal stem cells (MSCs) into osteoblasts was examined. Materials and Methods: Bone marrow cells collected from ……..Wistar rat's femor and flowcytometrywere used to identify them. In the experimental group (n=…..) MSCs treatment was done with various concentrations of saffron extract (i.e.0.5, 1, 1.5, and 2 mg/ml). Cytotoxic effect of saffron extract was evaluated using MTT assay and its aqueous extract effect on cell differentiation was investigated by means of Alizarin staining and alkaline phosphates activity. Results: Flowcytometry results confirmed the presence of stem cells using CD44 antibody. MTT assay results showed that the extract concentration of 1.5 mg/ml resulted in the death of 50 percent of stem cells derived from therats’ bone marrow during 24 hours (P<0.001). Alizarin staining showed saffron aqueous extract increased osteogenic s cell differentiation in a dose dependent manner in 21 days. (The maximum cell differentiation achieved by700 μg/ml concentration). Besides, higher alkaline phosphates activity was evident in the experimental group compared to the control group (n=……) in the 14th day (P<0.001). Conclusion: According to the findings of the current study, MSCs derived from the rat's bone marrow transform into osteoblasts when treated with saffron aqueous extract.